Ruxolitinib treatment in patients with polycythemia vera reduces JAK2 variant allele frequency and improves symptom burden and hematocrit control

Background: In RESPONSE/RESPONSE-2, ruxolitinib was superior to best available therapy (BAT) in patients with polycythemia vera (PV). Objective: Report a post hoc pooled RESPONSE/RESPONSE-2 analysis. Design: RESPONSE/RESPONSE-2 were randomized, open-label phase III trials. Adults with hydroxyurea-resistant/intolerant PV were randomized 1:1 to ruxolitinib or BAT; crossover to ruxolitinib was allowed after primary analysis. Methods: JAK2V617F allele burden, hematocrit control, and Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS) were assessed. Results: Among 371 patients, mean JAK2V617F allele burden declined from baseline (ruxolitinib, 66.1%; crossover, 69.5%) through week 208 (41.4%; 37.1%). Significantly more ruxolitinib versus BAT patients achieved hematocrit control at week 28 (62.0% vs 18.2%; p < 0.0001) and ⩾50% reduction in MPN-SAF TSS at week 16 (48.7% vs 18.0%; p < 0.0001). Conclusion: Patients receiving ruxolitinib experienced decreased JAK2V617F allele burden, durable hematocrit control, and better symptom improvements versus BAT, reinforcing ruxolitinib clinical benefit. Trial registration: RESPONSE: https://clinicaltrials.gov/study/NCT01243944; RESPONSE-2: https://clinicaltrials.gov/study/NCT02038036.